Professional Documents
Culture Documents
2 MECHANISM OF CATALYSIS
From the early 1970s, cyclodextrins have been extensively studied for its encapsulation properties and used
as binding sites in supramolecular catalyst.[2] Cyclodextrins have rigid ring structure, hydrophilic surface, and
hydrophobic cavity on the inside; therefore, they are
capable of binding organic molecules in aqueous solution. In 1978, with the background knowledge that
the hydrolysis of m-tert-butylphenyl acetate is accelerated in the presence of 2-benzimidazoleacetic acid and
alpha-cyclodextrin,[9] Brewslow et al. developed a catalyst based on a beta-cyclodextrin carrying two imidazole groups. This cyclodextrin catalytic system mimics
ribonuclease A by its use of a neutral imidazole and an
imidazolium cation to selective cleave cyclic phosphate
substrates. The rate of the reaction is catalyzed 120 times
faster, and unlike a hydrolysis by simple base NaOH that
gives a 1:1 mixture of the products, this catalysts yield a
99:1 selectivity for one compound.[5]
In 1993, Rebek et al. developed the rst self-assemble
capsule[10] and in 1997 the so-called tennis ball structure was used to catalyze a Diels-Alder reaction.[11] Selfassembled molecules have an advantage over crown ether
and cyclodextrin in that they can capture signicant larger
molecules or even two molecules at the same time. In
the following decades, many research groups, such as
Makoto Fujita, Ken Raymond, and Jonathan Nitschke,
developed cage-like catalysts also from molecular selfassembly principle.
In 2002, Sanders and coworkers published the use of
dynamic combinatorial library technique to construct a
receptor[12] and in 2003 they employed the technique to
develop a catalyst for Diels-Alder reaction.[13]
Mechanism of catalysis
Although high raise in eective concentration is observed, molecules that employ this mode of catalysis have
tiny rate acceleration compared to that of enzymes. A
proposed explanation is that in a container the substrates
2.1 Orienting reactive and labile groups
are not as tightly bound as in enzyme. The reagents have
room to wiggle in a cavity and so the entropic eect might
A supramolecular host could bind to a guest molecule
not be as important. Even in the case of enzymes, compuin such a way that the guests labile group is positioned
tational studies have shown that the entropic eect might
close to the reactive group of the host. The proximity
also be overestimated.[17]
of the two groups enhances the probability that the reaction could occur and thus the reaction rate is increased. Examples of molecules that work via this mechaThis concept is similar to the principle of preorganization nism are Rebeks tennis ball and Fujitas octahedral
which states that complexation could be improved if the complex.[11][18]
binding motifs are preorganized in a well-dened position
so that the host does not require any major conformational change for complexation.[15] In this case, the cat- 2.3 Stabilizing transition state
alyst is preorganized such that no major conformational
changes is required for the reaction to occur. A notable Supramolecular catalysts can accelerate reactions not
example of catalysts that employ this mechanism is Jean- only by placing the two reactants in close proximity but
Marie Lehns crown ether.[14] In addition, catalysts based also by stabilizing the transition state of the reaction and
on functionalized cyclodextrins often employ this mode reducing activation energy.[16]:89 While this fundamental
principle of catalysis is common in small molecule or hetof catalysis.[16]:88
Three common modes of catalysis are described here.
3.1
Design approach
20 amino acids.
3.2
needs to be measured directly and also quickly. To develop a high-throughput screen, substrates could be designed to change color or release a uorescent product
selec- upon reaction. For example, Crabtree and coworkers utilized this method in screening for a hydrosylation catalysts for alkene and imine.[23] Unfortunately the prerequisite for such substrates narrow down the range of reactions for study.[20]
A diagram depicting a use of transition state analog selection approach to select a catalytic antibody.
3.3
4 Prominent
examples
supramolecular catalysts
of
A problem with transition state analogue selection approach is that catalytic activity is not a screening criteria.
TSAs do not necessarily represent real transition states 4.1 Diederichs pyruvate oxidase mimic
and so a catalyst obtained from screening could just be
the best receptor for a TSA but is not necessarily the best In nature, pyruvate oxidase employs two cofactors
catalyst. To circumvent this problem, catalytic activity thiamine pyrophosphate (ThDP) and Flavin adenine din-
4.3
A self-assemble gallium catalyst developed by Ken Raymond accelerates Nazarov cyclization by stabilizing the cationic transition
state. The structure drawn here shows only one ligand for simplicity sake, but there are six ligands on the edges of the tetrahedral complex.
5 Supramolecular inhibitors
Supramolecular containers do not only have an application in catalysis but also in the opposite, namely, inhibition. A container molecule could encapsulate a guest
molecule and thus subsequently renders the guest unreactive. A mechanism of inhibition could either be that the
substrate is completely isolated from the reagent or that
the container molecule destabilize the transition state of
the reaction.
An asymmetric [2+2] photoaddition catalyst based on a tetrahedral palladium complex developed by Makoto Fujita. The catalyst has chiral diamine auxiliaries that induces the asymmetric
change in the cavity.
4.5
7 See also
Supramolecular Chemistry
Host-Guest Chemistry
Molecular Encapsulation
Articial enzyme
Asymmetric catalysis
8 References
6.1
Product inhibition
6.2
6.3
Syntheses of large complex catalysts are time and resource consuming. An unexpected deviation from the
design could be disastrous. Once a catalyst is discovered,
modication for further adjustment could be so syntheti- [11] Rebek, J. Jr; Kang, J. (1997). Acceleration of a Diels
cally challenging that it is easier to study the poor catalyst
Alder Reaction by a Self-Assembled Molecular Capsule.
Nature 385 (661): 5052. doi:10.1038/385050a0.
than to improve it.[21]
[12] Sanders, J. K. M.; Otto, S.; Furlan, R. L. E. (2002). Selection and Amplication of Hosts From Dynamic Combinatorial Libraries of Macrocyclic Disuldes. Science
297 (5581): 590593. doi:10.1126/science.1072361.
PMID 12142534.
[13] Otto, S.; Brisig, B.; Sanders, J. K. M. (2003). Selection
and Amplication of a Catalyst from a Dynamic Combinatorial Library. Angewandte Chemie International Edition 42 (11): 12701273. doi:10.1002/anie.200390326.
[14] Lehn, J.; Sirlin, C. (1978). Molecular Catalysis: Enhanced Rates of Thiolysis with High Structural and Chiral
Recognition in Complexes of a Reactive Macrocyclic Receptor Molecule. Chemical Communications (21): 949
951. doi:10.1039/C39780000949.
[15] Cram, D. J. (1988).
The Design of Molecular
Hosts, Guests, and Their Complexes. Angewandte
Chemie International Edition 27 (8): 10091020.
doi:10.1002/anie.198810093.
[16] Beer, P.; Gale, P. A.; Smith, D. K. (1999). Supramolecular Chemistry. New York: Oxford University Press. ISBN
0-19-850447-0.
[17] Warshel, A.; Aaqvist, J. (1993). The Design of Molecular Hosts, Guests, and Their Complexes. Chemical Reviews 93 (7): 25232544. doi:10.1021/cr00023a010.
[18] Fujita, M.; Yoshizawa, M.; Tamura, M. (2006). DielsAlder in Aqueous Molecular Hosts: Unusual Regioselectivity and Ecient Catalysis. Science 312 (5771): 251
254. doi:10.1126/science.1124985.
[19] Sanders, J. K. M.; Walter, C. J.; Anderson, H.
L. (1993). Exo-Selective Scceleration of an Intermolecular DielsAlder Reaction by a Trimeric Porphyrin Host. Chemical Communications (5): 458460.
doi:10.1039/C39930000458.
[20] Motherwell, W. B.; Bingham, M. J.; Six, Y. (2001).
Recent Progress in the Design and Synthesis of Articial Enzymes. Tetrahedron 57 (22): 46634686.
doi:10.1016/S0040-4020(01)00288-5.
[21] Sanders, J. K. M. (1998). Supramolecular Catalysis in Transition. Chemistry - A European Journal 4 (8): 13781383.
doi:10.1002/(SICI)15213765(19980807)4:8<1378::AIDCHEM1378>3.0.CO;2-3.
[22] Houk, K. N.; Kiss, G.; elebi-lm, N.; Moretti, R.;
Baker, D. (2013). Computational Enzyme Design.
Angewandte Chemie International Edition 52 (22): 5700
5725. doi:10.1002/anie.201204077.
[23] Crabtree, R. H.; Cooper, A. C.; McAlexander, L. H.; Lee,
D.-H.; Torres, M. T. (1998). Reactive Dyes as a Method
for Rapid Screening of Homogeneous Catalysts. Journal
of the American Chemical Society 120 (38): 99719972.
doi:10.1021/ja9818607.
[24] Lehn, J.; Huc, I. (1997).
Virtual Combinatorial Libraries: Dynamic Generation of Molecular and
Supramolecular Diversity by Self-Assembly. PNAS 94
(6): 21062110. doi:10.1073/pnas.94.6.2106.
REFERENCES
9.1
Text
9.2
Images
9.3
Content license